What is the role of IgA in the pathogenesis of Iga Vasculitis?
Many cases of IgAV occur following a respiratory infection, for which IgA is important for mucosal immunity. IgA plays a pivotal role in the pathogenesis of IgAV. There are two subclasses of IgA, IgA1 and IgA2. IgA1 accounts for 80% to 90% of serum IgA, but only 50% of secretory IgA. IgAV is associated with the deposition of IgA1and not IgA2. Notably, renal-limited IgA nephropathy (Berger disease) involves IgA1 exclusively as well.
For both IgAV and Berger disease, investigators have found that the hinge-region O-linked glycans of IgA1 are deficient in galactose and end with N -acetylgalactosamine (GalNAc). Antiglycan antibodies may recognize the GalNAc moiety on aberrant IgA1 molecules, leading to IC formation that is deposited in tissues and activates the alternative complement pathway. In addition, IgA can bind to mesangial cells in the kidney, leading to proliferation and release of proinflammatory cytokines. This kidney receptor binds IgA1 at its hinge region more readily when IgA1 is deficient in galactose. Patients with IgAV and Berger disease have had immunohistochemistry studies confirming deposition of galactose-deficient IgA1 in the kidney (in contrast, patients with lupus nephritis with IgA deposition did not show evidence of galactose-deficient IgA1 in the kidney).
